Dudel et al. (1989, Brain Res. 481: 215–220) demonstrated direct gating of an ion channel by glutamate in the arthropod, Schistocerca gregaria (locust) leg muscle.
Glutamate-gated chloride channels, or H-receptors, have been identified in arthropod nerve and muscle (Lingle et al, 1981, Brain Res. 212: 481–488; Horseman et al., 1988, Neurosci. Lett. 85: 65–70; Wafford and Sattelle, 1989, J. Exp. Bio. 144: 449–462; Lea and Usherwood, 1973, Comp. Gen. Parmacol. 4: 333–350; and Cull-Candy, 1976, J. Physiol. 255: 449–464).
Additionally, glutamate-gated chloride channels have been cloned from the soil nematode Caenorhabditis elegans (Cully et al., 1994, Nature 371: 707–711; see also U.S. Pat. No. 5,527,703 and Arena et al., 1992, Molecular Brain Research. 15: 339–348) and Drosophila melanogaster (Cully et al., 1996, J. Biol. Chem. 271: 20187–20191).
Raymond et al. (2000, Neuroreport 11: 2695–2701) disclose detection of GluCl channels in dorsal median neurons in Periplanta americana (cockroach).
Invertebrate glutamate-gated chloride channels are important targets for the widely used avermectin class of anthelmintic and insecticidal compounds. The avermectins are a family of macrocyclic lactones originally isolated from the actinomycete Streptomyces avermitilis. The semisynthetic avermectin derivative, ivermectin (22,23-dihydro-avermectin B1a), is used throughout the world to treat parasitic helminths and insect pests of man and animals. The avermectins remain the most potent broad spectrum endectocides exhibiting low toxicity to the host. After many years of use in the field, there remains little resistance to avermectin in the insect population. The combination of good therapeutic index and low resistance strongly suggests that the glutamate-gated chloride (GluCl) channels remain good targets for insecticide development.
Despite the identification of the aforementioned cDNA clones encoding GluCl channels, it would be advantageous to identify additional invertebrate genes encoding GluCl channels in order to allow screening to identify novel GluCl channel modulators that may have insecticidal, mitacidal and/or nematocidal activity for animal health or crop protection. The present invention addresses and meets these needs by disclosing isolated nucleic acid molecules which express a Schistocerca americana GluGl channel wherein expression of grasshopper GluCl cRNA in Xenopus oocytes or other appropriate host cell results in an active GluCl channel. Heterologous expression of a Schistocerca americana (grasshopper) GluCl channels will allow the pharmacological analysis of compounds active against parasitic invertebrate species relevant to animal and human health. Such species include worms, fleas, tick, and lice. Heterologous cell lines expressing an active GluCl channel can be used to establish functional or binding assays to identify novel GluCl channel modulators that may be useful in control of the aforementioned species groups.